Data values presented in the figures of the article 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling'

Duivenvoorden, Raphaël
Jacobs, M.M.E.

This collection contains the data values that are presented in the figures and supplementary figures of the publication : 'Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling' (Cell Reports, 2024, https://doi.org/10.1016/j.celrep.2024.114664). The files include the data values that are used to generate the figures and supplementary figures, the figure legends to explain what the data values represent and the figures themselves. Abstract: Trained immunity is characterized by histone modifications and metabolic changes in innate immune cells following exposure to inflammatory signals, leading to heightened responsiveness to secondary stimuli. Although our understanding of the molecular regulation of trained immunity has increased, the role of adaptive immune cells herein remains largely unknown. Here, we show that T cells modulate trained immunity via CD40-TRAF6 signaling. CD40-TRAF6 inhibition modulates functional, transcriptomic and metabolic reprogramming, and modifies histone 3 lysine 4 trimethylation associated with trained immunity. Besides in vitro studies, we reveal that single nucleotide polymorphisms in the proximity of CD40 are linked to trained immunity responses in vivo, and that combining CD40-TRAF6 inhibition with CTLA4-Ig-mediated co-stimulatory blockade induces long-term graft acceptance in a murine heart transplantation model. Combined, our study reveals that trained immunity is modulated by CD40-TRAF6 signaling between myeloid and adaptive immune cells and that this can be leveraged for therapeutic purposes.